Extracorporeal Rewarming Is Associated With Increased Survival Rate in Severely Hypothermic Patients With Preserved Spontaneous Circulation.

Treatment recommendations for rewarming patients in severe accidental hypothermia with preserved spontaneous circulation have a weak evidence due to the absence of randomized clinical trials. We aimed to compare the outcomes of extracorporeal versus less-invasive rewarming of severely hypothermic patients with preserved spontaneous circulation. We conducted a multicenter retrospective study. The patient population was compiled based on data from the HELP Registry, the International Hypothermia Registry, and a literature review. Adult patients with a core temperature <28°C and preserved spontaneous circulation were included. Patients who underwent extracorporeal rewarming were compared with patients rewarmed with less-invasive methods, using a matched-pair analysis. The study population consisted of 50 patients rewarmed extracorporeally and 85 patients rewarmed with other, less-invasive methods. Variables significantly associated with survival included: lower age; outdoor cooling circumstances; higher blood pressure; higher PaCO 2 ; higher BE; higher HCO 3 ; and the absence of comorbidities. The survival rate was higher in patients rewarmed extracorporeally ( p = 0.049). The relative risk of death was twice as high in patients rewarmed less invasively. Based on our data, we conclude that patients in severe accidental hypothermia with circulatory instability can benefit from extracorporeal rewarming without an increased risk of complications.

Successful Pre-Rewarming Resuscitation after Cardiac Arrest in Severe Hypothermia: A Retrospective Cohort Study from the International Hypothermia Registry.

The aim of our study is to investigate successful pre-rewarming resuscitation after hypothermic cardiac arrest (HCA). The hypothermic heart may be insensitive to defibrillation when core temperature is below 30 °C and after successful defibrillation, sinus rhythm often returns into ventricular fibrillation. Recurrent defibrillation attempts may induce myocardial injury. Discrepancy exists concerning pre-rewarming defibrillation between the guidelines of the European Resuscitation Council and American Heart Association. The International Hypothermia Registry (IHR) gathers hypothermia cases. The primary outcome was survival. Secondary outcomes were the characteristics of defibrillation, the effect of Adrenaline administration under 30 °C, and the duration of CPR. Of the 239 patients, eighty-eight were in cardiac arrest at arrival of the rescue team. Successful pre-rewarming resuscitation was obtained in 14 patients. The outcome showed: seven deaths, one vegetative state, two patients with reversible damage, and four patients with full recovery. A total of five patients had a shockable rhythm, and defibrillation was successful in four patients. The response rate to Adrenaline was reported as normal in six patients. There were no statistically significant differences in the presence of a shockable rhythm, the success of defibrillation, and the effect on Adrenaline administration between the survivors and non-survivors. Successful resuscitation in severe hypothermia is possible before active rewarming and arrival in the hospital, thus improving the chance of survival.

Hypothermic Cardiac Arrest - Retrospective cohort study from the International Hypothermia Registry.

AIM: The International Hypothermia Registry (IHR) was created to increase knowledge of accidental hypothermia, particularly to develop evidence-based guidelines and find reliable outcome predictors. The present study compares hypothermic patients with and without cardiac arrest included in the IHR. METHODS: Demographic, pre-hospital and in-hospital data, method of rewarming and outcome data were collected anonymously in the IHR between 2010 and 2020. RESULTS: Two hundred and one non-consecutive cases were included. The major causeof hypothermia was mountain accidents, predominantly in young men. Hypothermic Cardiac Arrest (HCA) occurred in 73 of 201 patients. Core temperature was significantly lower in the patients in cardiac arrest (25.0 vs. 30.0 °C, p < 0.001). One hundred and fifteen patients were rewarmed externally (93% with ROSC), 53 by extra-corporeal life support (ECLS) (40% with ROSC) and 21 with invasive internal techniques (71% with ROSC). The overall survival rate was 95% for patients with preserved circulation and 36% for those in cardiac arrest. Witnessed cardiac arrest and ROSC before rewarming were positive outcome predictors, asphyxia, coagulopathy, high potassium and lactate negative outcome predictors. CONCLUSIONS: This first analysis of 201 IHR patients with moderate to severe accidental hypothermia shows an excellent 95% survival rate for patients with preserved circulation and 36% for HCA patients. Witnessed cardiac arrest, restoration of spontaneous circulation, low potassium and lactate and absence of asphyxia were positive survival predictors despite hypothermia in young, healthy adults after mountaineering accidents. However, accidental hypothermia is a heterogenous entity that should be considered in both treatment strategies and prognostication.

S-nitroso human serum albumin as a nitric oxide donor in drug-eluting vascular grafts: Biofunctionality and preclinical evaluation.

Currently available synthetic small diameter vascular grafts reveal low patency rates due to thrombosis and intimal hyperplasia. Biofunctionalized grafts releasing nitric oxide (NO) in situ may overcome these limitations. In this study, a drug-eluting vascular graft was designed by blending polycaprolactone (PCL) with S-nitroso-human-serum-albumin (S-NO-HSA), a nitric oxide donor with prolonged half-life. PCL-S-NO-HSA grafts and patches were fabricated via electrospinning. The fabrication process was optimized. Patches were characterized in vitro for their morphology, drug release, biomechanics, inflammatory effects, cell proliferation, and expression of adhesion molecules. The selected optimized formulation (8%PCL-S-NO-HSA) had superior mechanical/morphological properties with high protein content revealing extended NO release (for 28 days). 8%PCL-S-NO-HSA patches significantly promoted endothelial cell proliferation while limiting smooth muscle cell proliferation. Expression of adhesion molecules (ICAM-1, VCAM-1) and pro-inflammatory macrophage/cytokine markers (CD80, IL-1α, TNF-α) was significantly reduced. 8%PCL-S-NO-HSA patches had superior immunomodulatory properties by up-regulating anti-inflammatory cytokines (IL-10) and M2 macrophage marker (CD163) at final time points. Grafts were further evaluated in a small rodent model as aortic implants up to 12 weeks. Grafts were assessed by magnetic resonance imaging angiography (MRI) in vivo and after retrieval by histology. All grafts remained 100 % patent with no signs of thrombosis or calcification. 8%PCL-S-NO-HSA vascular grafts supported rapid endothelialization, whereas smooth muscle cell proliferation was hampered in earlier phases. This study indicates that 8%PCL-S-NO-HSA grafts effectively support long-term in situ release of bioactive NO. The beneficial effects observed can be promising features for long-term success of small diameter vascular grafts. STATEMENT OF SIGNIFICANCE: Despite extensive research in the field of small diameter vascular graft replacement, there is still no appropriate substitute to autografts yet. Various limitations are associated with currently available synthetic vascular grafts such as thrombogenicity and intimal hyperplasia. Therefore, developing new generations of such conduits has become a major focus of research. One of the most significant signaling molecules that are involved in homeostasis of the vascular system is nitric oxide. The new designed nitric-oxide eluting vascular grafts described in this study induce rapid surface endothelialization and late migration of SMCs into the graft wall. These beneficial effects have potential to improve current limitations of small diameter vascular grafts.

Arteriovenous access in hemodialysis: A multidisciplinary perspective for future solutions.

In hemodialysis, vascular access is a key issue. The preferred access is an arteriovenous fistula on the non-dominant lower arm. If the natural vessels are insufficient for such access, the insertion of a synthetic vascular graft between artery and vein is an option to construct an arteriovenous shunt for punctures. In emergency situations and especially in elderly with narrow and atherosclerotic vessels, a cuffed double-lumen catheter is placed in a larger vein for chronic use. The latter option constitutes a greater risk for infections while arteriovenous fistula and arteriovenous shunt can fail due to stenosis, thrombosis, or infections. This review will recapitulate the vast and interdisciplinary scenario that characterizes hemodialysis vascular access creation and function, since adequate access management must be based on knowledge of the state of the art and on future perspectives. We also discuss recent developments to improve arteriovenous fistula creation and patency, the blood compatibility of arteriovenous shunt, needs to avoid infections, and potential development of tissue engineering applications in hemodialysis vascular access. The ultimate goal is to spread more knowledge in a critical area of medicine that is importantly affecting medical costs of renal replacement therapies and patients' quality of life.

Novel, digital, chest drainage system in cardiac surgery.

BACKGROUND: A new, self-contained, digital, continuous pump-driven chest drainage system is compared in a randomized control trial to a traditional wall-suction system in cardiac surgery. METHODS: One hundred and twenty adult elective cardiac patients undergoing coronary artery bypass graft and/or valve surgery were randomized to the study or control group. Both groups had similar pre/intra-operative demographics: age 67.8 vs 67.0 years, Euroscore 2.3 vs 2.2, and body surface area 1.92 vs 1.91 m2 . Additionally, a satisfaction assessment score (0-10) was performed by 52 staff members. RESULTS: Given homogenous intra-operative variables, total chest-tube drainage was comparable among groups (566 vs 640 mL; ns), but the study group showed more efficient fluid collection during the early postoperative phase due to continuous suction (P = .01). Blood, cell saver transfusions and postoperative hemoglobin values were similar in both groups. The study group experienced drain removal after 29.8 vs 38.4 hours in the control group (ns). Seven crossovers from the Study to the Control group were registered but no patient had drain-related complications. The Personnel Satisfaction Assessment scored above 5 for all questions asked. CONCLUSIONS: The new, digital, chest drainage system showed better early drainage of the chest cavity and was as reliable as conventional systems. Quicker drain removal might impact on intensive care unit (ICU) stay and reduce costs. Additional advantages are portable size, battery operation, patient mobility, noiseless function, digital indications and alarms. The satisfaction assessment of the new system by the staff revealed a higher score when compared to the traditional wall suction chest drainage system.

Slow versus fast rewarming after hypothermic circulatory arrest: effects on neuroinflammation and cerebral oedema.

OBJECTIVES: Among the factors that could determine neurological outcome after hypothermic circulatory arrest (HCA) rewarming is rarely considered. The optimal rewarming rate is still unknown. The goal of this study was to investigate the effects of 2 different protocols for rewarming after HCA on neurological outcome in an experimental animal model. METHODS: Forty-four Sprague Dawley rats were cooled to 19 ± 1°C body core temperature by cardiopulmonary bypass (CPB). HCA was maintained for 60 min. Animals were randomized to receive slow (90 min) or fast (45 min) assisted rewarming with CPB to a target temperature of 35°C. After a total of 90 min of reperfusion in both groups, brain samples were collected and analysed immunohistochemically and with immunofluorescence. In 10 rats, magnetic resonance imaging was performed after 2 and after 24 h to investigate cerebral perfusion and cerebral oedema. RESULTS: Interleukin 6, chemokine (C-C motif) ligand 5, intercellular adhesion molecule 1 and tumour necrosis factor α in the hippocampus are significantly less expressed in the slow rewarming group, and microglia cells are significantly less activated in the slow rewarming group. Magnetic resonance imaging analysis demonstrated better cerebral perfusion and less water content in brains that underwent slow rewarming at 2 and 24 h. CONCLUSIONS: Slow rewarming after HCA might be superior to fast rewarming in neurological outcome. The present experimental study demonstrated reduction in the inflammatory response, reduction of inflammatory cell activation in the brain, enhancement of cerebral blood flow and reduction of cerebral oedema when slow rewarming was applied.

Wilderness Medical Society Clinical Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update.

To provide guidance to clinicians, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and a balance between benefits and risks/burdens according to the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. This is the 2019 update of the Wilderness Medical Society Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2014 Update.

Risk of Burns During Active External Rewarming for Accidental Hypothermia.

This article describes 3 incidents in which therapeutic or experimental warming of cold individuals caused first- to third-degree burns to the skin. Mechanisms for these injuries are considered. We conclude that active external rewarming of the trunk of a cold patient in the field can be administered safely and burn risk reduced if 1) manufacturer instructions are followed; 2) insulation is placed between the skin the and heat source; and 3) caregivers make regular efforts to observe heated skin for possible pending burn injury. Direct inspection is mandatory for the skin of areas that are on top of a heat source when the patient is lying on the heat source.

Effect of implantation site on outcome of tissue-engineered vascular grafts.

OBJECTIVE: Vascular prostheses for small caliber bypass grafts in cardiac and vascular diseases or for access surgery are still missing. Poly (Ɛ-caprolactone) (PCL) has been previously investigated by our group and showed good biocompatibility and mechanical properties in vitro and rapid endothelialisation, cellular infiltration and vascularisation in vivo yielding optimal patency in the abdominal aortic position. The aim of the present study is to evaluate our PCL graft in the carotid position and to compare its outcome to the grafts implanted in the abdominal aortic position. METHODS: PCL grafts (1 mm ID/10 mm long) were implanted into the left common carotid artery in 20 Sprague-Dawley rats and compared to our previously published series of abdominal aortic implants. The animals were followed up to 3, 6, 12 and 24 weeks. At each time point, in vivo compliance, angiography and histological examination with morphology were performed. RESULTS: PCL grafts showed good mechanical properties and ease of handling. The average graft compliance was 14.5 ±â€¯1.7%/ mmHg compared to 7.8 ±â€¯0.9% for the abdominal position and 45.1 ±â€¯3.2%/ mmHg for the native carotid artery. The overall patency for the carotid position was 65% as compared to 100% in the abdominal position. Complete endothelialisation was achieved at 3 weeks and cell invasion was more rapid than in the aortic position. In contrast, intimal hyperplasia (IH) and vascular density were less pronounced than in the aortic position. CONCLUSION: Our PCL grafts in the carotid position were well endothelialised with early cellular infiltration, higher compliance, lower IH and calcification compared to the similar grafts implanted in the aortic position. However, there was a higher occlusion rate compared to our abdominal aorta series. Anatomical position, compliance mismatch, flow conditions may answer the difference in patency seen.

Successful Defibrillation of Four Hypothermic Patients with Witnessed Cardiac Arrest.

BACKGROUND: Because of the limited evidence available, recommendations for defibrillation of hypothermic patients vary among published guidelines. AIM: To report successful defibrillation of four severely hypothermic patients with witnessed cardiac arrest. RESULTS: During a four-year period from 2014 to 2017, four of five hypothermic patients admitted to our institution with a history of sudden, unexpected ventricular fibrillation (core temperature: 24°C-27°C) were successfully defibrillated. Restoration of spontaneous circulation (ROSC) was possible after a single defibrillator shock (two patients) or during prolonged advanced life support cardiopulmonary resuscitation (two patients). Our patients and additional cases identified in the literature indicate that successful defibrillation is predominantly found in hypothermic patients with a core temperature above 24°C. CONCLUSIONS: Our data demonstrate that successful defibrillation and ROSC are possible in selected patients with severe accidental hypothermia and are perhaps more common than widely believed. These findings are of particular importance for mountain and wilderness rescue missions when transfer of an arrested patient to the nearest hospital providing extracorporeal rewarming is not possible. An automatic external defibrillator should be part of the medical equipment on any search or mountain rescue mission, in which the victim may have sustained accidental hypothermia.

Temperature Variation After Rewarming from Deep Hypothermic Circulatory Arrest Is Associated with Survival and Neurologic Outcome.

Therapeutic hypothermia is recommended by international guidelines after cardio-circulatory arrest. However, the effects of different temperatures during the first 24 hours after deep hypothermic circulatory arrest (DHCA) for aortic arch surgery on survival and neurologic outcome are undefined. We hypothesize that temperature variation after aortic arch surgery is associated with survival and neurologic outcome. In the period 2010-2014, a total of 210 consecutive patients undergoing aortic arch surgery with DHCA were included. They were retrospectively divided into three groups by median nasopharyngeal temperature within 24 hours after rewarming: hypothermia (<36°C; n = 65), normothermia (36-37°C; n = 110), and hyperthermia (>37°C; n = 35). Multivariate stepwise logistic and linear regressions were performed to determine whether different temperature independently predicted 30-day mortality, stroke incidence, and neurologic outcome assessed by cerebral performance category (CPC) at hospital discharge. Compared with normothermia, hyperthermia was independently associated with a higher risk of 30-day mortality (28.6% vs. 10.9%; odds ratio [OR] 2.8; 95% confidence interval [CI], 1.1-8.6; p = 0.005), stroke incidence (64.3% vs. 9.1%; OR 9.1; 95% CI, 2.7-23.0; p = 0.001), and poor neurologic outcome (CPC 3-5) (68.8% vs. 39.6%; OR 4.8; 95% CI, 1.4-8.7; p = 0.01). No significant differences were demonstrated between hypothermia and normothermia. Postoperative hypothermia is not associated with a better outcome after aortic arch surgery with DHCA. However, postoperative hyperthermia (>37°C) is associated with high stroke incidence, poor neurologic outcome, and increased 30-day mortality. Target temperature management in the first 24 hours after surgery should be evaluated in prospective randomized trials.

The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry.

Accidental hypothermia could be listed as an 'orphan disease,' since mild hypothermia is common but has no severe medical consequences, whereas severe hypothermia is rare and life-threatening. In order to increase our knowledge, find new outcome predictors, and propose better guidelines for the treatment of deep accidental hypothermia victims, we created the International Hypothermia Registry (IHR: https://www.hypothermia-registry.org), which will allow us to gather a large number of cases in order to achieve statistical significance and issue evidence-based recommendations.

Biodegradable and plasma-treated electrospun scaffolds coated with recombinant Olfactomedin-like 3 for accelerating wound healing and tissue regeneration.

Three-dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM-related protein Olfactomedin-like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4-fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in-growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds.

Accidental hypothermia-an update : The content of this review is endorsed by the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).

BACKGROUND: This paper provides an up-to-date review of the management and outcome of accidental hypothermia patients with and without cardiac arrest. METHODS: The authors reviewed the relevant literature in their specialist field. Summaries were merged, discussed and approved to produce this narrative review. RESULTS: The hospital use of minimally-invasive rewarming for non-arrested, otherwise healthy, patients with primary hypothermia and stable vital signs has the potential to substantially decrease morbidity and mortality for these patients. Extracorporeal life support (ECLS) has revolutionised the management of hypothermic cardiac arrest, with survival rates approaching 100 % in some cases. Hypothermic patients with risk factors for imminent cardiac arrest (temperature <28 °C, ventricular arrhythmia, systolic blood pressure <90 mmHg), and those who have already arrested, should be transferred directly to an ECLS-centre. Cardiac arrest patients should receive continuous cardiopulmonary resuscitation (CPR) during transfer. If prolonged transport is required or terrain is difficult, mechanical CPR can be helpful. Delayed or intermittent CPR may be appropriate in hypothermic arrest when continuous CPR is impossible. Modern post-resuscitation care should be implemented following hypothermic arrest. Structured protocols should be in place to optimise pre-hospital triage, transport and treatment as well as in-hospital management, including detailed criteria and protocols for the use of ECLS and post-resuscitation care. CONCLUSIONS: Based on new evidence, additional clinical experience and clearer management guidelines and documentation, the treatment of accidental hypothermia has been refined. ECLS has substantially improved survival and is the treatment of choice in the patient with unstable circulation or cardiac arrest.

External Saphenous Vein Support Mesh Does Not Interfere With Transit-Time Flow Measurement on Venous Coronary Bypass Conduit: Clinical Confirmation.

A 65-year-old patient underwent double coronary artery bypass grafting using the left internal thoracic artery on the left anterior descending coronary artery and nitinol alloy mesh [external Saphenous Vein Support (eSVS)]-covered saphenous vein graft to the right posterior descending coronary artery. Transit-time flow measurements (TTFMs) were obtained on meshed and bare parts of the vein graft. There was no difference in TTFM parameters (flow, pulsatility index, and diastolic fraction values) obtained from the eSVS mesh-covered and the uncovered parts of the venous graft. This observation confirms that eSVS mesh does not interfere with TTFM on venous coronary bypass conduits.

Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site.

Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some extent, be useful to forecast results for vascular prostheses. We compared biological and histological responses to scaffolds in different implantation sites. Polycaprolactone (PCL), paclitaxel-loaded PCL (PCL-PTX) and dexamethasone-loaded PCL (PCL-DXM) electrospun scaffolds were implanted subcutaneously and in an infrarenal abdominal aortic model in rats for up to 12 weeks. At the conclusion of the study, a histological analysis was performed. Cellular graft invasion revealed differences in the progression of cellular infiltration between PCL-PTX and PCL/PCL-DXM groups in both models. Cell infiltration increased over time in the aortic model compared to the subcutaneous model for all groups. Cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation in all groups and models over time. Macrophages and giant cells increased in the PCL aortic model; whereas in the subcutaneous model these cell types increased only after three weeks or even decreased in the drug-eluting PCL groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. The subcutaneous implant model can be used for screening, especially when drug-eluting effects are studied. However, major histological differences were observed in cell type reaction and depth of cell penetration compared to the aortic model. Our results demonstrate that the implantation site is a critical determinant of the biological response.